Cardiovascular disease (CVD) is one of the major causes of death in western world.
Elevated serum total and/or LDL (low density lipoprotein) cholesterol and triacyl-glycerol levels, as well as low ratio of HDL (high density lipoprotein) cholesterol to LDL cholesterol, are some of the major risk factors for CVD. Recently also serum levels of apolipoprotein B 100 (apo B) has been shown to be a reliable CVD risk marker. In most developed countries a substantial amount of the population have serum cholesterol levels not within the recommended levels. One of the first steps in improving the serum lipid profile is changes in life style including changes in diet and exercise. It seems, however, difficult to change dietary habits and to follow dietary recommendations. Thus, there is a clear need for solutions beyond regular diet and lifestyle changes by which serum lipid profile can be improved.
Food products enriched with components having cholesterol lowering effect beyond normal nutrition have been commercially available for some time. Representative examples are food products enriched with plant stanol or sterol fatty acid esters. Stanol fatty acid esters and the cholesterol lowering effects thereof are disclosed in U.S. Pat. No. 5,502,045 as well as a suitable method for their preparation. Dietary intake of 2 to 3 g/day of plant stanols is reported to lower serum LDL cholesterol levels in man up to 14% without affecting HDL cholesterol levels. The amount of atherogenic apolipoprotein B particles in blood is also decreased, thus reducing the risk of CVD.
Some proteins have also been used to improve serum lipid profile. Proteins that have been shown to lower serum total and/or LDL cholesterol include e.g. soy protein (Anderson J. W., et al, New Engl. J. Medicine 1995 333 (5) 276-282), whey protein (Nagaoka et al., Agric. Biol. Chem. 1991 (55) 813-818) and wheat gluten (EP 0 790 060 Al). FDA has approved a health claim about the role of soy protein in reducing the risk of CVD by lowering blood cholesterol levels. In order to qualify for this health claim, a food must contain at least 6.25 grams of soy protein per serving, the amount being one-fourth of the effective level of 25 grams per day, and be included in a diet low in saturated fat and cholesterol.
EP 0 669 835 B1 describes a hypocholesterolemic dietary composition containing soy protein and sitosterols, the sitosterols and soy protein being of natural origin and having synergistic cholesterol lowering effect. The composition is used for example as tablets, capsules or syrups. Effective daily intakes of the composition are not given Also EP 1 046 396 A2 describes a composition containing soy protein, preferably soy protein isolate or soy protein concentrate, and plant sterols having synergistic cholesterol lowering effect. The synergistic effect is achieved, when both the soy protein and plant sterols are administered in amounts that would be sufficient to induce cholesterol-lowering activity of each of the administered compound alone. WO 01/37681 describes a composition containing phytosterols and an isolated water-soluble protein, such as soy protein or caseinate, and optionally also an emulsifier. The composition can be utilized in food products, where the composition improves mouthfeel and stability of the sterol containing foods. No improved cholesterol lowering effect compared to the effect achieved with phytosterols alone is attributed to this composition.
U.S. 6,113,972 describes a phytosterol protein complex, where the complex increases the bioavailability of the phytosterols. No cholesterol lowering effect is attributed to the protein part of this composition, but the protein functions only as a carrier to the phytosterols. In fact, any fat binding protein can be used in this complex and especially egg proteins are preferred. A composition containing plant sterols/stanols and an emulsifier, mixed into a protein-containing product, is described in WO 00/33669. The protein does not have any cholesterol lowering effect in this composition either, but it aids in the formation of the emulsion.
Protein hydrolysates have been shown to have greater serum cholesterol lowering effect than the corresponding unhydrolyzed proteins (Sugano et al., J. Nutr. 1990 (120) 977-985). The cholesterol lowering effect of protein hydrolysates might be attributed to certain peptides, for example such as found from bovine milk β-lactoglobulin by Nagaoka et al. (Biochem. Biophys. Res. Commun., 2001, 281(1), 11-17), but this still remains to be proven by well-controlled clinical and/or animal studies. EP 0 790 060 A1 discloses a protein hydrolysate/phospholipid complex for improving lipid metabolism, where the complex contains 10% or more bound phospholipids, especially lecithin or enzyme modified lecithin. Lipid profile improving effect, especially LDL-cholesterol lowering and HDL-cholesterol raising effect of lecithin is well known in prior art (for example Childs et al., 1981, Atherosclerosis 38, 217). In the complex according to EP 0 790 060 A1 certain bound phospholipids (lecithin or enzyme modified lecithin) are believed to remarkably contribute to the lipid metabolism improving effect of the complex.
The current literature and especially FDA's interim approval of a health claim for plant sterols have increased the interest of the food industry in supplementing foods with plant sterols. Indeed, many such food items have recently been introduced into the market. It is assumed that new plant sterol containing foods will appear into the market rapidly.
The active launching of new plant sterol containing foods has raised a concern that a part of the population may have higher daily intake of plant sterols than what is needed to obtain an optimal cholesterol lowering effect. Short-term high intake of plant sterols has not been shown to be harmful. However, there is no data on possible long-term side effects of ingestion of high daily amounts (>3g/day or higher) of plant sterols. Furthermore, there is currently not a clear understanding of the biological impact of the increased serum level and thus higher systemic availability of plant sterols caused by increased intake from sterol enriched foods, especially foods enriched with unsaturated plant sterols.
There is a clear need for improved solutions by which the serum lipid profile can be improved, e.g. elevated serum total and/or LDL cholesterol levels reduced and/or HDL cholesterol levels increased and/or triacylglycerol levels reduced and/or apolipoprotein B levels reduced. Compositions based on combinations of active ingredients having enhanced, additive or even synergistic effects compared to the active ingredients alone are needed. It would also be desirable to obtain meaningful and sustainable improvements in the serum lipid profile with lower daily intake of the individual active ingredients than what is obtainable with the intakes currently used. Possible adverse effects of the active ingredients such as possible impact on fat-soluble antioxidants and other digestive discomforts could thus be reduced. Incorporation of the active ingredients into a wider range of food products without adverse effects on organoleptic properties is also needed. The present invention provides compositions meeting these requirements.